Robb Krumlauf

Last updated
Robb Krumlauf
CitizenshipAmerican
Alma mater Vanderbilt University, Ohio State University
Known forprogression in the field of developmental biology and his progression on the current understanding of Hox genes
Scientific career
Fields Cell biology; developmental biology
InstitutionsBeatson Institute for Cancer Research, Fox Chase Cancer Center, Francis Crick Institute, University of Kansas School of Medicine, University of Missouri at Kansas Dental School, Stowers Institute for Medical Research
Doctoral students Nancy Papalopulu [1]

Robb Krumlauf is an American developmental biologist. He is best known for researching the Hox family of transcription factors. He is most interested in understanding the role of the Hox genes in the hindbrain and their role in areas of animal development, such as craniofacial development. Krumlauf worked with a variety of renowned scientists in the field of developmental biology throughout his time researching Hox genes. [2]

Contents

Early life and education

Robb was born in Ohio and raised in Ohio and New York. He graduated from Vanderbilt University in 1970 with a degree in chemical engineering. He later went to The Ohio State University and received his PhD in developmental biology in 1979. He has since gone on to be a researcher and professor. [3]

Career

After Krumlauf had completed his formal education, he was hired at Beatson Institute for Cancer Research along with the Fox Chase Cancer Center. In 1985, he moved to London to work at what is now known as the Francis Crick Institute. This institution is one of the most well-known biomedical research centers in the world. At the turn of the millennium, Krumlauf came back to the United States and resided in Missouri. He has since taken on three occupations and has been a professor at the University of Kansas, the University of Kansas School of Medicine, and the University of Missouri at Kansas Dental School. He is now the director of the Stowers Institute for Medical Research. [3]

Research

Krumlauf researched Hox gene complexes in both mice and Drosophila in 1989. The complexes in both species were compared in order to determine if the gene complexes between these two species may have arisen from a common ancestor. The data shows alignment of these complexes and comparable relative position of genes. This research demonstrates the relationship between Homeobox genes in Drosophila (insects) and mice (metazoans). [4]

Krumlauf examined Hox-2 gene expression dependence on the differentiation pathway in 1991. The study shows Hox-2 gene expression has a clear reliance on the endoderm pathway the cells follow, which suggests a dependence on Hox-2 expression on the type and degree of differentiation in different cells. This publication also solidified the importance of retinoic acid on Hox-2 expression. [5]

In 1996, Krumlauf researched the abnormal migration of motor neurons in mice that lack Hoxb-1. [6] In this study, Krumlauf knew that the vertebrate hindbrain segments into rhombomeres, and that this was responsible for controlling the arrangement of motor neurons in the hindbrain. His research with mutant mouse embryos found that the absence of Hoxb-1 lead to changes in rhombomere 4 (r4) identity. This mutation causes a difference in migration patterns in r4, which demonstrates that Hoxb-1 is plays a role in the regulation of migratory properties of motor neurons present in the hindbrain. [6]

Krumlauf has manipulated the expression of Hox genes in many ways throughout his career in order to observe variations in development amongst certain animals. For example, in 2013, Krumlauf and his team configured mutant animals with a double-mutant cluster of HoxA-HoxB genes in their neural crest cells. In these mutant animals, they observed a bone that resembled the dentary along with an attachment of neo-muscle. This helped Krumlauf to determine the HoxB genes are able to enhance a phenotype that was directly caused by the deletion of a HoxA cluster. This helped the research group to assess the cooperation between different clusters of Hox genes. Through the use of mutant clusters of HoxA-HoxB genes, Krumlauf and his team were able to visualize how the suppression of one of the Hox genes, with amplification of another type of Hox genes, can be critical in the proper development of an animal. The example shown in this study was the variation in craniofacial development when certain Hox genes are suppressed. [7]

In 2014, Krumlauf examined Hox gene expression in comparison to hindbrain segmentation. Gnathostomes were used in this research in an attempt to determine how primitive the relationship between Hox gene expression and segmentation of the hindbrain is. The data concluded that there is clear correlation between Hox expression and hindbrain segmentation. The use of gnathostomes shows this trait to be ancient, with origin at the base of vertebrates. [8]

Krumlauf is best known for his progression in the field of animal developmental biology and his progression on the current understanding of Hox genes. Hox genes are known for laying out the basic body structures of a wide variety of animals. Hox genes control a variety of regulatory interactions in the hindbrain which leads to segmentation in animals.[5] After many years of research on the importance of Hox genes through manipulation trials, Krumlauf studied the variations of Hox genes between vertebrates and invertebrates in 2017. He notes that Hox gene expression was found in even the most primitive vertebrates, such as the sea lamprey. This Hox gene expression has been maintained across phylogenetically dissimilar vertebrates. However, this is not the case for invertebrates. Krumlauf studied the Hox genes present in chordates and found these invertebrates to lack hindbrain segmentation. He did find that chordates still had conserved some of the aspects of the Hox gene network. This includes things such as the use of retinoic acid in establishing Hox-gene domains. [9]

Krumlauf’s publications can be used to better understand the role of Hox genes within many species of animals. His research has also helped to express the importance of suppression and regulation of individual Hox genes.

Additional publications

"Patterning the vertebrate neuraxis" (1996) This publication examines segmentation and long-range signaling from organizing centers to interpret the role these principles play in the patterning of a vertebrate neuraxis. [10]

"Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes" (1997) This investigation seeks to observe the Hox clusters present in a teleost fish, Fugu rubripes. Four different Hox complexes were discovered within Fugu rubripes. The data shows the Hox clusters in Fugu to be widely variant with respect to length. At least nine genes in the Hox complex has been lost in Fugu when compared to present mammalian complexes. This data demonstrates that gene loss of prototypical Hox clusters is a defining feature in both tetrapod and fish evolution. [11]

"'Shocking' developments in chick embryology: electroporation and in ovo gene expression" (1999) This paper focuses on new approaches to the analysis of gene expression through the use of electroporation. This work focuses on the protocol for electroporation, how it can be applied to differing organisms, and the future experiments that could be conducted through the use of electroporation. [12]

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the cephalic flexure. In human embryonic development, the rhombomeres are present by day 29.

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

In evolutionary developmental biology, homeosis is the transformation of one organ into another, arising from mutation in or misexpression of certain developmentally critical genes, specifically homeotic genes. In animals, these developmental genes specifically control the development of organs on their anteroposterior axis. In plants, however, the developmental genes affected by homeosis may control anything from the development of a stamen or petals to the development of chlorophyll. Homeosis may be caused by mutations in Hox genes, found in animals, or others such as the MADS-box family in plants. Homeosis is a characteristic that has helped insects become as successful and diverse as they are.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<span class="mw-page-title-main">Retinoic acid</span> Metabolite of vitamin A

Retinoic acid (used simplified here for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that mediates the functions of vitamin A1 required for growth and development. All-trans-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.

<i>Ciona intestinalis</i> Species of ascidian

Ciona intestinalis is an ascidian, a tunicate with very soft tunic. Its Latin name literally means "pillar of intestines", referring to the fact that its body is a soft, translucent column-like structure, resembling a mass of intestines sprouting from a rock. It is a globally distributed cosmopolitan species. Since Linnaeus described the species, Ciona intestinalis has been used as a model invertebrate chordate in developmental biology and genomics. Studies conducted between 2005 and 2010 have shown that there are at least two, possibly four, sister species. More recently it has been shown that one of these species has already been described as Ciona robusta. By anthropogenic means, the species has invaded various parts of the world and is known as an invasive species.

<span class="mw-page-title-main">HOXB6</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B6 is a protein that in humans is encoded by the HOXB6 gene.

<span class="mw-page-title-main">Homeobox A1</span> Protein-coding gene in humans

Homeobox protein Hox-A1 is a protein that in humans is encoded by the HOXA1 gene.

<span class="mw-page-title-main">HOXC8</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C8 is a protein that in humans is encoded by the HOXC8 gene.

<span class="mw-page-title-main">HOXD13</span> Protein

Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene. This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms.

<span class="mw-page-title-main">HOXB1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B1 is a protein that in humans is encoded by the HOXB1 gene.

<span class="mw-page-title-main">HOXB2</span> Protein-coding gene in humans

Homeobox protein Hox-B2 is a protein that in humans is encoded by the HOXB2 gene.

<span class="mw-page-title-main">HOXD3</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-D3 is a protein that in humans is encoded by the HOXD3 gene.

<span class="mw-page-title-main">HOXB13</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B13 is a protein that in humans is encoded by the HOXB13 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">HOXB8</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B8 is a protein that in humans is encoded by the HOXB8 gene.

<span class="mw-page-title-main">HOXC11</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C11 is a protein that in humans is encoded by the HOXC11 gene.

<span class="mw-page-title-main">Nancy Papalopulu</span> Professor of Developmental Neuroscience

Athanasia Papalopulu is a Wellcome Trust senior research fellow and Professor of Developmental Neuroscience in the School of Biological Sciences, University of Manchester.

Segmentation is the physical characteristic by which the human body is divided into repeating subunits called segments arranged along a longitudinal axis. In humans, the segmentation characteristic observed in the nervous system is of biological and evolutionary significance. Segmentation is a crucial developmental process involved in the patterning and segregation of groups of cells with different features, generating regional properties for such cell groups and organizing them both within the tissues as well as along the embryonic axis.

<span class="mw-page-title-main">Hox genes in amphibians and reptiles</span>

Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.

References

  1. ↑ Papalopoulou, Athanasia (1991). Analysis of vertebrate homeobox containing genes. ucl.ac.uk (PhD thesis). University of London. OCLC   1170168705. EThOS   uk.bl.ethos.815786. Open Access logo PLoS transparent.svg
  2. 1 2 3 4 "Krumlauf Lab | Stowers Institute for Medical Research". www.stowers.org.
  3. 1 2 3 "Robb Krumlauf". www.nasonline.org. Retrieved 2020-04-19.
  4. ↑ Graham, A.; Papalopulu, N.; Krumlauf, R. (1989-05-05). "The murine and Drosophila homeobox gene complexes have common features of organization and expression". Cell. 57 (3): 367–378. doi:10.1016/0092-8674(89)90912-4. ISSN   0092-8674. PMID   2566383. S2CID   22259601.
  5. ↑ Papalopulu, N; Lovell-Badge, R; Krumlauf, R (1991-10-25). "The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos". Nucleic Acids Research. 19 (20): 5497–5506. doi:10.1093/nar/19.20.5497. ISSN   0305-1048. PMC   328948 . PMID   1682879.
  6. 1 2 Studer, M.; Lumsden, A.; Ariza-McNaughton, L.; Bradley, A.; Krumlauf, R. (19–26 December 1996). "Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1". Nature. 384 (6610): 630–634. Bibcode:1996Natur.384..630S. doi:10.1038/384630a0. ISSN   0028-0836. PMID   8967950. S2CID   4317559.
  7. ↑ Vieux-Rochas, Maxence; Mascrez, Bénédicte; Krumlauf, Robb; Duboule, Denis (2013-10-01). "Combined function of HoxA and HoxB clusters in neural crest cells". Developmental Biology. 382 (1): 293–301. doi: 10.1016/j.ydbio.2013.06.027 . ISSN   1095-564X. PMID   23850771.
  8. ↑ Parker, Hugo J.; Bronner, Marianne E.; Krumlauf, Robb (2014-10-23). "A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates". Nature. 514 (7523): 490–493. Bibcode:2014Natur.514..490P. doi:10.1038/nature13723. ISSN   1476-4687. PMC   4209185 . PMID   25219855.
  9. ↑ Parker, Hugo J.; Krumlauf, Robb (November 2017). "Segmental arithmetic: summing up the Hox gene regulatory network for hindbrain development in chordates". Wiley Interdisciplinary Reviews. Developmental Biology. 6 (6): e286. doi:10.1002/wdev.286. ISSN   1759-7692. PMID   28771970. S2CID   3849662.
  10. ↑ Lumsden, A.; Krumlauf, R. (1996-11-15). "Patterning the vertebrate neuraxis". Science. 274 (5290): 1109–1115. Bibcode:1996Sci...274.1109L. doi:10.1126/science.274.5290.1109. ISSN   0036-8075. PMID   8895453. S2CID   10891464.
  11. ↑ Aparicio, S.; Hawker, K.; Cottage, A.; Mikawa, Y.; Zuo, L.; Venkatesh, B.; Chen, E.; Krumlauf, R.; Brenner, S. (1997). "Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes". Nature Genetics. 16 (1): 79–83. doi:10.1038/ng0597-79. ISSN   1061-4036. PMID   9140399. S2CID   12434208.
  12. ↑ Itasaki, N.; Bel-Vialar, S.; Krumlauf, R. (1999). "'Shocking' developments in chick embryology: electroporation and in ovo gene expression". Nature Cell Biology. 1 (8): E203–207. doi:10.1038/70231. ISSN   1465-7392. PMID   10587659. S2CID   205096435.
  13. ↑ "Robert Eugene Krumlauf". American Academy of Arts & Sciences. 2023-05-26. Retrieved 2023-05-26.
  14. ↑ "Society for Developmental Biology | Resource". www.sdbonline.org. Retrieved 2020-04-19.
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