Stem cells

Overview

Some of the most important problems facing biology today involve the mechanisms by which post-embryonic stem cells are established, maintained, and ultimately recruited to differentiate at particular times and places in the adult. These cells are essential for normal development, and understanding their biology has translational importance in the context of cancer, senescence and tissue regeneration.

We use post-embryonic lineages of pigment cells to understand fundamental aspects of stem cell biology. These cells arise from the neural crest, which also contributes to numerous other tissues and organs, including neurons and glia of the peripheral nervous system and bone and cartilage of the craniofacial skeleton. Our work has identified different lineages of neural crest derived pigment cells with distinct behaviors and requirements.

embryo

adult

melanoma

Adult melanophore and iridophore stem cells

Melanophores are homologous to mammalian melanocytes and develop using the same genetic pathways. We showed that latent precursors to adult melanophores are found within the peripheral nervous system (as in mammals) and that these cells migrate to the skin beginning ~10 d post fertilization. ErbB receptor tyrosine kinase signaling is required to establish these stem cells, and we have identified several genes needed for their later recruitment, including puma, which encodes an alpha tubulin. Precursors to iridophores are also found within the peripheral nervous system.

 

 

  • Budi et al. 2011. PLoS Genetics 7:e1002044.    PDF   WEB
  • Budi et al. 2008. Development 135:2603–2614.   PDF   WEB
  • Larson et al. 2010. Developmental Biology 346:296–309.   PDF
  • Parichy et al. 2003.  Developmental Biology 256:242–257.   PDF   WEB
  • Mills et al. 2007. Development 134:1081–1090.   PDF   WEB

Development of adult melanophores (left) fails in the puma mutant (right)

Adult

melanophores

differentiating

over 18 h

Melanophore

precursor

migrating to the skin

Precursor detaching from peripheral nerve

Lineages of adult pigment cells.

A different origin of adult xanthophores and the differential dependence of adult pigment cell lineages on thyroid hormone

 

In contrast to melanophores and iridophores, we showed that many adult xanthophores develop directly from embryonic xanthophores, which  transiently lose their pigment, proliferate, and ultimate re-differentiate during adult pattern formation. Using transgenic and mutational approaches we showed that thyroid hormone promotes xanthophore differentation and proliferation. Yet, thyroid hormone has the opposite effect on melanophores, repressing the adult melanophore population. Normal pigment cell lineage development, and pattern formation, are thus critically dependent on the right balance of thyroid hormone.

Excess xanthophore division in hyperthyroid mutant

  • McMenamin et al. 2014. Science 345:1358–1361.   PDF   WEB
  • Parichy & Spiewak. 2014. Pigment Cell and Melanoma Research 28:31–50.   PDF   WEB

wild-type

hyperthyroid mutant

control

thyroid-ablated

Current projects include

  • controls and lineages of additional pigment cell classes across Danio, especially red erythrophores
  • genomic mechanisms underlying cell lineage specific responses to thyroid hormone
  • studies of thyroid hormone in melanoma susceptibility using zebrafish
  • forward and reverse genetic analyses in zebrafish and other danios to understand the evolution of  lineage behaviors

erythrophores

 

PARICHY LAB

Department of Biology

University of Virginia

Physical and Life Sciences Building

Charlottesville VA 22904

 

 

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