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ZFIN ID: ZDB-PERS-970213-1
Krumlauf, Robb
Affiliation: Krumlauf Lab
Address: Stowers Institute for Medical Research 1000 East 50th Street Kansas City, MO 64110 USA
Country: United States
Phone: (816) 926-4051
ORCID ID: 0000-0001-9102-7927

I am deeply interested in understanding the regulatory information and associated molecular mechanisms encoded in vertebrate genomes which guide the formation and elaboration of the basic body plan. My research has been aimed at dissecting regulatory circuits which control how organs and tissues are generated along embryonic axes form from similar cellular building blocks. A deep understanding of such processes is critical to understand morphogenesis. While there is amazing similarity in many processes between vertebrates how variations in their regulation leads to diversity in evolution is poorly understood. My group has use head development and Hox genes as model systems to understand patterning mechanisms and regulatory networks in hindbrain segmentation and craniofacial development. Hox genes play critical roles in regulating regional diversity in many tissues so our goal is to build a basis for comparing regulatory pathways that pattern many elements of the basic body plan in development, disease and evolution.

The vertebrate hindbrain and its relationship to head development is a good model system for understanding fundamental mechanisms of patterning and morphogenesis during development, disease and evolution. The hindbrain is a highly conserved complex co-ordination center in the vertebrate CNS. The formation of regional diversity in the hindbrain is achieved through a process of segmentation, which ultimately gives rise to well-defined regions of the adult brain. This segmental organization is critical for patterning of the cranial neural crest which generates most of the bone and connective tissues of head and facial structures. The Hox family of transcription factors is coupled to this process and provides a molecular framework for specifying the unique identities of hindbrain segments and facial structures. Because the segmental processes of head development are highly conserved among vertebrates, comparative studies between different species have greatly enhanced our ability to build a picture of the regulatory cascades that control early head development. Through comparative studies in lamprey, zebrafish and mice we are beginning to address the interesting question of when ordered domains of Hox expression were coupled to hindbrain segmentation in chordate origins and what signaling pathways/regulatory mechanisms were involved.

Biography: I received a BE in chemical engineering from Vanderbilt University (1970) and a PhD in developmental biology from Ohio State University (1979). I did postdoctoral research with Shirley Tilghman at the Fox Chase Cancer Center and established my group at England’s National Institute for Medical Research at Mill Hill, London, now a part of the Francis Crick Institute, where I became head of the Division of Developmental Neurobiology. I was the the Founding Scientific Director of the Stowers Institute (2000-2019) and am currently an Investigator and Scientific Director Emeritus of the Stowers Institute. I hold secondary faculty appointments at the University of Missouri at Kansas City Dental School and the University of Kansas Medical Center Department of Anatomy and Cell Biology.

Prummel, K.D., Hess, C., Nieuwenhuize, S., Parker, H.J., Rogers, K.W., Kozmikova, I., Racioppi, C., Brombacher, E.C., Czarkwiani, A., Knapp, D., Burger, S., Chiavacci, E., Shah, G., Burger, A., Huisken, J., Yun, M.H., Christiaen, L., Kozmik, Z., Müller, P., Bronner, M., Krumlauf, R., Mosimann, C. (2019) A conserved regulatory program initiates lateral plate mesoderm emergence across chordates. Nature communications. 10:3857
Parker, H.J., De Kumar, B., Green, S.A., Prummel, K.D., Hess, C., Kaufman, C.K., Mosimann, C., Wiedemann, L.M., Bronner, M.E., Krumlauf, R. (2019) A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates. Nature communications. 10:1189
De Kumar, B., Parker, H.J., Paulson, A., Parrish, M.E., Zeitlinger, J., Krumlauf, R. (2017) Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis. Developmental Biology. 432(1):151-164
De Kumar, B., Parker, H.J., Paulson, A., Parrish, M.E., Pushel, I., Singh, N.P., Zhang, Y., Slaughter, B.D., Unruh, J.R., Florens, L., Zeitlinger, J., Krumlauf, R. (2017) HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets. Genome research. 27(9):1501-1512
McEllin, J.A., Alexander, T.B., Tümpel, S., Wiedemann, L.M., Krumlauf, R. (2016) Analyses of fugu hoxa2 genes provide evidence for subfunctionalization of neural crest cell and rhombomere cis-regulatory modules during vertebrate evolution. Developmental Biology. 409(2):530-42
Parker, H.J., Bronner, M.E., Krumlauf, R. (2014) A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates. Nature. 514(7523):490-3
Trainor, P.A. and Krumlauf, R. (2000) Patterning the cranial neural crest: hindbrain segmentation and Hox gene plasticity. Nature reviews. Neuroscience. 1(2):116-124
Manzanares, M., Trainor, P.A., Nonchev, S., Ariza-McNaughton, L., Brodie, J., Gould, A., Marshall, H., Morrison, A., Kwan, C.-T., Sham, M.-H., Wilkinson, D.G., and Krumlauf, R. (1999) The role of kreisler in segmentation during hindbrain development. Developmental Biology. 211(2):220-237
Pöpperl, H., Bienz, M., Studer, M., Chan, S., Aparicio, S., Brenner, S., Mann, R., and Krumlauf, R. (1995) Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell. 81:1031-1042
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