# Oocyte polarity and BMP-mediated dorsoventral patterning

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2024 · $769,179

## Abstract

Abstract:
 Bone Morphogenetic Protein (BMP) signaling directs the development of multiple organs and tissues,
and is the cause of multiple congenital and adult diseases, including cardiovascular defects, kidney disease,
pulmonary hypertension, and is important in medical applications in orthopedics, endodontics, and tissue
engineering. BMP heterodimers exhibit consistently higher signaling activity to BMP homodimers in a multitude
of contexts. Understanding how BMP heterodimers signal more effectively will lead to their more successful use
in tissue engineering, bone repair, regeneration, and therapeutics. The zebrafish offers a paradigm of exclusive
BMP heterodimer signaling in patterning the dorsoventral embryonic axis as a morphogen, with different levels
specifying distinct cell types. This grant revealed specialized functions of the BMP Type I receptors in the
heterodimer signaling mechanism, with Acvr1 exclusively providing the kinase activity to transduce the signal,
whereas surprisingly the Bmpr1 kinase is dispensable. Intriguingly, Bmp2 homodimers were also found to require
the heteromeric Type I receptor complex of Acvr1 and Bmpr1, indicating that the role of the heterodimer is to
bring these two Type I receptors together, which elicits higher signaling activity than homomeric Type I signaling
complexes. This proposal investigates the nature of the subfunctionalized roles of the Type I receptors in
signaling and their trafficking in signal regulation through in vivo live imaging analysis, taking advantage of the
large translucent zebrafish embryo. This grant demonstrated that the BMP gradient is interpreted into three cell
fate domains by concentration thresholds of signaling and not by signal duration or gradient slope thresholds.
Further studies are proposed to understand the outcomes of gradient thresholds and its regulation over time.
 In most vertebrates, polarity of the egg determines polarity of the embryo and establishes the embryonic
dorsal-ventral axis and germ line. Egg polarity originates during oogenesis with the first polarized structure in
vertebrate oocytes, the Balbiani body (Bb), a large, membrane-less structure conserved from insects to
mammals typically composed of mitochondria and ribonucleoproteins, destined to the vegetal pole of the oocyte
and egg. Although fundamental to forming the major axes of most vertebrate embryos, vertebrate oocyte polarity
has been little studied. In zebrafish, a key factor Bucky ball (Buc) was discovered that establishes the Bb and
oocyte polarity. Buc is a highly disordered protein that can undergo a phase transition to form amyloid-like fibers
in vitro. The role of Buc in aggregating the Bb will be studied through unique buc hypomorphic alleles identified
in the previous period that reveal its distinct functions in oocyte polarity, axis formation, and germ line
development. From proteomics analysis of the Bb in the previous period, new highly disordered proteins with
predicted self-ag...

## Key facts

- **NIH application ID:** 10842736
- **Project number:** 2R35GM131908-06
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mary C. Mullins
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $769,179
- **Award type:** 2
- **Project period:** 2019-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842736

## Citation

> US National Institutes of Health, RePORTER application 10842736, Oocyte polarity and BMP-mediated dorsoventral patterning (2R35GM131908-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10842736. Licensed CC0.

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