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Christopher V. Wright, D. Phil.

Louise B. McGavock Chair
Professor of Cell and Developmental Biology
Director, Vanderbilt University Program in Developmental Biology
Associate Director, Vanderbilt Center for Stem Cell Biology
AAAS Fellow - 2012

Molecular embryology /vertebrate embryogenesis /transcription factors/intercellular signaling.
Lab Website

Faculty Senate

Dr. Wright is chairing the Vanderbilt Faculty Senate Strategic Planning and Academic Freedom committee for 2018-2019 academic year.

Research Description

Our long-term goal is to provide insight into the molecular mechanisms responsible for the coordinated development of complex organ systems, which has relevance to human congenital birth defects, and cryptic susceptibilities to disease or syndromes. The vertebrate body is built by a series of progressively refined decisions.  First, long-range decisions have to be made on how the “head to tail” axis is formed.  Then, specific tissue territories must acquire the potential to form each organ (brain, spinal cord, lungs, liver, gut, pancreas) in the right place at the right time. They must all become hooked up to each other properly, attached to the blood supply, and also become innervated.  The transcription-factor–based (TF-based) and epigenetically guided gene-regulatory networks controlling these decisions can be dissected by various methods.  A predominant view is that chromatin is progressively opened up from a closed state, to allow access to genes and their cis-reguatory regions.  For example, enhancers may be released from heterochromatin by the ability of pioneer TFs to crack open the condensed chromatin state.  Thereafter, regulatory cofactors are recruited to those accessible chromatin domains.  Cis-regulatory DNA regions, or enhancers, can be differentially marked by post-translational modifications (PTMs) of their histones and other chromatin proteins. They are initially marked equivalently by PTMs that are repressive or activating with respect to the transcriptional state of the locus, causing a so-called “bivalent” condition.  Addition or removal of the marking leads to predominance in one or the other type of marking, to close down or allow transcription to occur. These processes operate in carefully orchestrated tiers of action.  Genes allowed to activate, through the action of the first-arriving pioneer TFs, can produce other TFs or regulatory proteins.  These proteins are themselves then able to search the genome and land on other chromosome locations to cause activation or repression of (small or large) sets of target genes.  Combinatorial action with the pioneer factors is often encountered.


All of these processes can be analyzed using either single-cell or bulk methods such as ATAC-Seq, single-molecule-FISH, epigenetic analysis, real-time/time-lapse video- and super-resolution microscopy, 3D tissue-clearing immunolabeling approaches, and many others.  We are working on how the pancreas forms, and on how these genetic and epigenetic mechanisms control how lineage decisions are made, first in choosing the pancreas fate over stomach, liver, duodenal, and bile duct fates.  We work on this problem in human tissues during the stages in which strong predisposition to type I autoimmune diabetes can emerge, and in mouse tissues where we can undertake precision genetic and other types of perturbational manipulation, as well as select specific cell types for molecular-genetic, biochemical and physical interrogation.  We work on:


• The principal genes that control acquisition of the pancreatic organ fate.

• The “run program” that allows a surprisingly small number of progenitors in the initial pancreas anlagen to turn into a much larger organ with precisely arranged endocrine- and exocrine-functioning cells.

• The production of endocrine cells of the pancreas within a dynamic epithelial niche, which we have recently redefined in several foundational publications.

• How the pancreatic epithelium forms this niche and slowly becomes resolved to a simpler ductal state

• How endocrine cells are progressively produced from endocrine-biased (lineage-primed) mitotic progenitors, then on to post-mitotic cells that depart the epithelium and cluster into islets of Langerhans.

• Human TF genes mutated in permanent neonatal diabetes & other diseases and tissue malformation.

• Cryptic epigenetic mis-programming.  For example, Mnx1 deficiency allows endocrine cells to continue their normal lineage program as insulin-producing beta cells, until a specific time postnatally when receiving some form of signal that causes rewiring of their GRNs, and a sudden and complete switch into somatostatin-producing delta cells.

More information

Postdoctoral Positions Available

To study pancreas formation and function using state of the art genome manipulation techniques in vivo in mouse (knockout, knockin, transgenic) and in vitro cell culture models.


Selected Publications