# Regulation of cell fates by the Bicaudal-C translational repressor

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $304,035

## Abstract

Abstract: Over the course of an animal’s lifetime, cell-fate decisions are continually being made that allow for
normal development and growth as well as the health of the adult organism. Cell-fate decisions require
precisely controlled temporal and spatial expression of particular proteins. In early vertebrate development and
certain adult cell types, such as those of the nervous system, this regulated protein expression relies heavily
on post-transcriptional mechanisms, particularly translational control. This proposal focuses on a conserved
RNA binding protein named Bicaudal-C (Bicc1) that functions in translational regulation and is essential for
normal vertebrate development. While it is established that Bicc1 is an RNA binding protein required for the
normal development and health of vertebrates, the cellular and molecular mechanisms by which Bicc1
performs these roles are largely unknown and thus represent a major gap in knowledge. In addition, because
several relevant Bicc1 target mRNAs have only recently been identified, their roles in vertebrate development
are also unknown, limiting the ability to connect Bicc1’s molecular functions to specific cell-fate decisions. The
long-term research goal is to define the molecular mechanisms by which developmentally important RNA
binding proteins select their target mRNAs and control mRNA expression to effect specific cell-fate decisions,
and to understand how defects in these processes contribute to cell dysfunction and organismal disease. The
central hypothesis is that Bicc1 selects particular target mRNAs through a complex RNA binding domain with
multiple independent RNA binding surfaces, and regulates translation via additional distinct regions yet to be
defined. This hypothesis is based on extensive research from the lab focused on defining how Bicc1 directs the
earliest, maternal stages of vertebrate development in the model organism Xenopus laevis. This work has
established Bicc1 as a paradigm for understanding how RNA binding proteins control mRNA translation to
direct complex cell-fate decisions. Building on extensive conceptual and technical progress over the past
decade, the Specific Aims will address the central hypothesis by: 1. Defining elements within Bicc1 target
mRNAs required for Bicc1 binding and translational regulation; 2. Determining the regions of Bicc1 that are
necessary and sufficient to selectively bind and contact mRNAs and to function in translational regulation.
These regions’ roles in embryogenesis will also be examined; and 3. Defining the roles of Bicc1 mRNA targets
in cell-fate decisions during vertebrate development. The research employs a rigorous and multidisciplinary
strategy incorporating RNA-protein biochemistry, unique translation-reporter assays, genome-enabled
approaches, reverse molecular genetics and embryology to define the molecular mechanisms by which the
conserved and disease-relevant RNA binding protein Bicc1 directs the earliest cell-fate decisions...

## Key facts

- **NIH application ID:** 10407579
- **Project number:** 5R01HD091921-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Michael D Sheets
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $304,035
- **Award type:** 5
- **Project period:** 2018-08-05 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407579

## Citation

> US National Institutes of Health, RePORTER application 10407579, Regulation of cell fates by the Bicaudal-C translational repressor (5R01HD091921-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10407579. Licensed CC0.

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