Michael Sheets

Biomolecular Chemistry Department

Molecular mechanisms regulating early vertebrate development

mdsheets@wisc.edu

(608) 262-9452

5260 Biochemistry Building
420 Henry Mall
Madison, WI 53706

Headshot

lab website:

https://bmolchem.wisc.edu/staff/sheets-michael-d/

focus groups:

Developmental Biology & Regenerative Medicine; RNA Biology

research description:

The highly regulated and selective translation of maternal mRNAs drives key cell-fate decisions during the earliest stages of animal development. Accumulating evidence reveals the importance of translational regulation to the formation and maintenance of internal organ systems during later development and in adults as well. While the importance of this regulation is incontrovertible, little work has focused on the underlying mechanisms that control the expression of mRNAs that encode key cell-fate regulators. Our recent findings in the model organism Xenopus laevis place us in a uniquely strong position to make advances in this research area particularly relevant to vertebrate organisms, including humans. We have shown that the developmental regulatory RNA binding protein Bicaudal-C (Bic-C) functions in the cell-type translational repression of maternal mRNAs that encode proteins that control vertebrate embryogenesis. For one of these targets, the Cripto-1 mRNA that encodes a co-receptor required for Nodal signaling, we have defined the Bic-C binding site, the first defined binding site for any Bic-C ortholog. We have also and shown that this site is functionally relevant to Bic-C-mediated cell-type specific translation repression. Currently we are combining RNA and protein biochemistry with unique embryological assays for translation regulation developed in my lab to address the molecular basis of Bic-C functions in vertebrate embryogenesis. In addition, recent evidence from a variety of vertebrate organisms, including humans, reveals a strong link between Bic-C and normal organogenesis and organ function. Thus our research addresses a key regulatory RNA binding protein Bic-C and its role in translational regulation during vertebrate development and in human disease.

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