EMX1

Last updated
EMX1
Identifiers
Aliases EMX1 , empty spiracles homeobox 1
External IDs OMIM: 600034 MGI: 95387 HomoloGene: 55799 GeneCards: EMX1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001040404
NM_004097

NM_010131

RefSeq (protein)

NP_004088

NP_034261

Location (UCSC) Chr 2: 72.92 – 72.94 Mb Chr 6: 85.16 – 85.18 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Corticogenesis in a mouse brain. Subplate neurons are coloured yellow. Corticogenesis in a wild-type mouse with captions in english copy.png
Corticogenesis in a mouse brain. Subplate neurons are coloured yellow.

Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene. [5] [6] The transcribed EMX1 gene is a member of the EMX family of transcription factors. The EMX1 gene, along with its family members, are expressed in the developing cerebrum (also known as the telencephalon). [7] EMX1 plays a role in specification of positional identity, the proliferation of neural stem cells, differentiation of layer-specific neuronal phenotypes and commitment to a neuronal or glial cell fate. [8]

Contents

Function

The precise function of the Emx1 transcription factor is not known, however its ubiquitous nature throughout corticogenesis suggests it may confer cellular identity to cortical neurons.

Emx -/- (mice that have had Emx1 gene knocked out) are still viable and display only slight defects. These defects are restricted to the forebrain. Histologically and molecularly, the structures of the cerebral cortex appear to be normal. The hippocampus in Emx1 -/- mice, however, is typically smaller. The major deficit in Emx1-/- mice is that they completely lack the corpus callosum.

Tissue distribution

Most of Emx1 transcript is detected in cell nuclei of the developing telencephalon, including the prospective cerebral cortex, olfactory bulbs and hippocampus. Emx1 is present in practically all cortical neurons during proliferation, migration, differentiation and maturation. However, the amount of Emx 1 varies. Emx1 first appears at E9.5 in its respective mRNA, until E11.5. After this, the Emx1 signal becomes particularly potent in the ventricular zone (VZ) until E17.5. At birth and shortly thereafter, Emx1 levels in layers V and VI as well as in the SP increase.

Telencephalic development

Emx1 and Emx2 each play a critical role in regulating dorsal telencephalic development and are amongst the earliest expressed pallial-specific genes. [8]

During embryonic development, the telencephalon is the birthplace of a diverse collection of neuronal and glial cells. These cells undergo varying patterns of cell migration in order to reach their final positions in what will become the mature cerebral cortex and basal ganglia. The embryonic telencephalon is subdivided into dorsal pallium and ventral subpallium. These two pallia become the mammalian cerebral cortex and basal ganglia, respectively.

The dorsal telencephalon is then further divided into:

Dorsal Telencephalic SubdivisionsBasic Developmental Role
Medial Pallium (MP)Gives rise to archicortex, including the hippocampus.
Dorsal Pallium (DP)Foundation of the neocortex.
Lateral Pallium (LP)Generates the olfactory cortex
Ventral Pallium (VP)Claustromygdaloid complex generated here.

Each of the aforementioned pallial domains will give rise to a distinct neuroanatomical region of the developed human brain.

The ventral telencephalon can also be subdivided into two distinguishable progenitor domains:

Ventral Telencephalic SubdivisionRole
Lateral Ganglionic Eminence (LGE)Generates the striatum.
Medial Ganglionic Eminence (MGE)Generates the pallidum.

The dorsal and ventral telencephalic domains can be distinguished embryonically through distinct gene expression patterns. These genes are regionally restricted and take part in identity specification of the area of the telencephalon in which they are expressed.

Developmental targets of the embryonic telencephalon. Future Developmental Structures of the Embryonic Telencephalon.svg
Developmental targets of the embryonic telencephalon.

Role in the mouse embryo

Emx1 expression has been shown to start from E9.5 (see gestational age). [9] In the developing mouse embryo, the Emx genes are expressed principally in extended regions of the developing rostral brain, including the cerebral cortex, olfactory bulbs and olfactory epithelium. Emx1 gene expression is constricted to the dorsal telencephalon.

From E9.5 until post-natal stages, Emx1 expression is associated with cortical neurogenesis, differentiation and migration, and synaptic connection generation. This suggests that Emx1 plays a crucial role in determining the identity of the developing cortex. Emx1 is not only limited to the telencephalon, rather it is also expressed in branchial patterns and in the apical ectodermal ridge of the developing limbs.

Developing forebrain

At E9.5, Emx1 expression can be witnessed within the dorsal telencephalon slightly anterior to the boundary between the diencephalon and telencephalon Emx1 is expressed in most cortical neurons within the developing telencephalon. [7]

Expression can be seen irrespective of whether the neurons are proliferating, migrating or differentiating. This means that in the developed cerebral cortex, the transcript for Emx1 is widely distributed. While distribution of the transcript may be seen throughout the developed cortex, the transcript intensity varies greatly according to developmental time. For example, the transcript for Emx1 is shown to be stronger in the ventricular zone (VZ) between E10.5 and E17.5. However, around birth and immediately thereafter, the Emx1 transcript is absent from the marginal zone (MZ), only becoming stronger in cortical layers V and VI as well as subset subplate (SP) neurons.

In cortical layers V and VI as well as the SP neurons, Emx1 might take part in development of early functional circuitry, as well as in defining specific cellular identities.

The distribution of Emx1 is so ubiquitous in the developing brain that in mid- and late-gestation embryos, as well as postnatal mice, it is found in cerebral cortex, olfactory bulbs, dentate gyrus and hippocampus. [7]

Regulation by Gli3

The Gli3 zinc finger transcription factor has been shown to play a role as a regulator of Emx1. In Gli3 Extra-toes mutants, the transcription factor Gli3 is mutated and as a result, Emx1 and Emx2 gene expression is lost. [8] [10]

Related Research Articles

<span class="mw-page-title-main">Cerebral cortex</span> Outer layer of the cerebrum of the mammalian brain

The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness. The cerebral cortex is part of the brain responsible for cognition.

The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

<span class="mw-page-title-main">Cerebrum</span> Large part of the brain containing the cerebral cortex

The cerebrum, telencephalon or endbrain is the largest part of the brain containing the cerebral cortex, as well as several subcortical structures, including the hippocampus, basal ganglia, and olfactory bulb. In the human brain, the cerebrum is the uppermost region of the central nervous system. The cerebrum develops prenatally from the forebrain (prosencephalon). In mammals, the dorsal telencephalon, or pallium, develops into the cerebral cortex, and the ventral telencephalon, or subpallium, becomes the basal ganglia. The cerebrum is also divided into approximately symmetric left and right cerebral hemispheres.

<span class="mw-page-title-main">GLI3</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.

<span class="mw-page-title-main">DAB1</span> Protein-coding gene in the species Homo sapiens

The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis. It docks to the intracellular part of the Reelin very low density lipoprotein receptor (VLDLR) and apoE receptor type 2 (ApoER2) and becomes tyrosine-phosphorylated following binding of Reelin to cortical neurons. In mice, mutations of Dab1 and Reelin generate identical phenotypes. In humans, Reelin mutations are associated with brain malformations and mental retardation. In mice, Dab1 mutation results in the scrambler mouse phenotype.

<span class="mw-page-title-main">Fibroblast growth factor 8</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 8(FGF-8) is a protein that in humans is encoded by the FGF8 gene.

<span class="mw-page-title-main">HOXA3</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-A3 is a protein that in humans is encoded by the HOXA3 gene.

<span class="mw-page-title-main">EMX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Emx2 is a protein that in humans is encoded by the EMX2 gene.

<span class="mw-page-title-main">LHX1</span> Protein-coding gene in the species Homo sapiens

LIM homeobox 1 is a protein that in humans is encoded by the LHX1 gene. This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells. It is also key in development of renal and urogenital systems and is required for normal organogenesis. A similar protein in mice is an essential regulator of the vertebrate head organizer.

<span class="mw-page-title-main">VAX1</span> Protein-coding gene in the species Homo sapiens

Ventral anterior homeobox 1 is a protein that in humans is encoded by the VAX1 gene.

<span class="mw-page-title-main">Ganglionic eminence</span>

The ganglionic eminence (GE) is a transitory structure in the development of the nervous system that guides cell and axon migration. It is present in the embryonic and fetal stages of neural development found between the thalamus and caudate nucleus.

<span class="mw-page-title-main">Pallium (neuroanatomy)</span> Layers of grey and white matter that cover the upper surface of the cerebrum in vertebrates

In neuroanatomy, pallium refers to the layers of grey and white matter that cover the upper surface of the cerebrum in vertebrates. The non-pallial part of the telencephalon builds the subpallium. In basal vertebrates the pallium is a relatively simple three-layered structure, encompassing 3–4 histogenetically distinct domains, plus the olfactory bulb.

<span class="mw-page-title-main">TBR1</span> Protein-coding gene in Homo sapiens

T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the TBR1 gene. This gene is also known by several other names: T-Brain 1, TBR-1, TES-56, and MGC141978. TBR1 is a member of the TBR1 subfamily of T-box family transcription factors, which share a common DNA-binding domain. Other members of the TBR1 subfamily include EOMES and TBX21. TBR1 is involved in the differentiation and migration of neurons and is required for normal brain development. TBR1 interacts with various genes and proteins in order to regulate cortical development, specifically within layer VI of the developing six-layered human cortex. Studies show that TBR1 may play a role in major neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and autism spectrum disorder (ASD).

<span class="mw-page-title-main">HOXA2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-A2 is a protein that in humans is encoded by the HOXA2 gene.

<span class="mw-page-title-main">DBX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein DBX2, also known as developing brain homeobox protein 2, is a protein that in humans is encoded by the DBX2 gene. DBX2 plays an important role in the development of the central nervous system, specifically in the development of the neural tube and brain. DBX2 is located on chromosome 12 and is approximately 36,000 base pairs long. DBX2 is predicted to enable DNA-binding transcription activity as well as being involved in the regulation of transcription by RNA polymerase II.

<span class="mw-page-title-main">Eomesodermin</span> Protein-coding gene in the species Homo sapiens

Eomesodermin also known as T-box brain protein 2 (Tbr2) is a protein that in humans is encoded by the EOMES gene.

Corticogenesis is the process during which the cerebral cortex of the brain is formed as part of the development of the nervous system of mammals including its development in humans. The cortex is the outer layer of the brain and is composed of up to six layers. Neurons formed in the ventricular zone migrate to their final locations in one of the six layers of the cortex. The process occurs from embryonic day 10 to 17 in mice and between gestational weeks seven to 18 in humans.

Cajal–Retzius cells are a heterogeneous population of morphologically and molecularly distinct reelin-producing cell types in the marginal zone/layer I of the developmental cerebral cortex and in the immature hippocampus of different species and at different times during embryogenesis and postnatal life.

<span class="mw-page-title-main">Ventricular zone</span> Transient embryonic layer of tissue containing neural stem cells

In vertebrates, the ventricular zone (VZ) is a transient embryonic layer of tissue containing neural stem cells, principally radial glial cells, of the central nervous system (CNS). The VZ is so named because it lines the ventricular system, which contains cerebrospinal fluid (CSF). The embryonic ventricular system contains growth factors and other nutrients needed for the proper function of neural stem cells. Neurogenesis, or the generation of neurons, occurs in the VZ during embryonic and fetal development as a function of the Notch pathway, and the newborn neurons must migrate substantial distances to their final destination in the developing brain or spinal cord where they will establish neural circuits. A secondary proliferative zone, the subventricular zone (SVZ), lies adjacent to the VZ. In the embryonic cerebral cortex, the SVZ contains intermediate neuronal progenitors that continue to divide into post-mitotic neurons. Through the process of neurogenesis, the parent neural stem cell pool is depleted and the VZ disappears. The balance between the rates of stem cell proliferation and neurogenesis changes during development, and species from mouse to human show large differences in the number of cell cycles, cell cycle length, and other parameters, which is thought to give rise to the large diversity in brain size and structure.

Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes, and subgranular zone radial astrocytes, among others.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000135638 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033726 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. "Entrez Gene: EMX1 empty spiracles homeobox 1".
  7. 1 2 3 Cecchi C, Boncinelli E (August 2000). "Emx homeogenes and mouse brain development". Trends Neurosci. 23 (8): 347–52. doi:10.1016/S0166-2236(00)01608-8. PMID   10906797. S2CID   45006292.
  8. 1 2 3 Schuurmans C, Guillemot F (February 2002). "Molecular mechanisms underlying cell fate specification in the developing telencephalon". Curr. Opin. Neurobiol. 12 (1): 26–34. doi:10.1016/S0959-4388(02)00286-6. PMID   11861161. S2CID   27988180.
  9. Frantz GD, Bohner AP, Akers RM, McConnell SK (February 1994). "Regulation of the POU domain gene SCIP during cerebral cortical development". J. Neurosci. 14 (2): 472–85. doi:10.1523/JNEUROSCI.14-02-00472.1994. PMC   6576830 . PMID   7905511.
  10. Theil T, Alvarez-Bolado G, Walter A, Rüther U (August 1999). "Gli3 is required for Emx gene expression during dorsal telencephalon development". Development. 126 (16): 3561–71. doi:10.1242/dev.126.16.3561. PMID   10409502.

Further reading