# Revealing how cytoskeletal dynamics form the early mammalian embryo

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $491,090

## Abstract

SUMMARY
Revealing the key events that specify the first differentiated cell lineages during mammalian development is key
to understand how the early embryo is organized to implant in the uterus and establish a pregnancy. The first
mammalian cell lineages comprise the pluripotent inner cell mass (ICM) that will form the fetus, and the outer
trophectoderm that will form the placenta. Yet, the mechanisms explaining how these lineages differentiate are
unclear. In many non-mammalian embryos, asymmetrically inherited cell-fate determinants specify lineage fate,
yet similar mechanisms are thought to be absent during early mammalian development.
We have established live-imaging approaches to study cell and molecular dynamics during early mouse
development. Recently, we identified a new role for intermediate filaments assembled by keratins in lineage
specification. Our studies reveal that keratin filaments are asymmetrically inherited precisely during the cell
divisions that physically segregate the future ICM and trophectoderm. Moreover, the inheritance of these
filaments by the outer daughter cells helps to specify their trophectoderm identity and promote their maturation.
Thus, our main hypothesis is that keratin filaments function as a new form of asymmetrically inherited factor
specifying the first trophectoderm cells during development. To test this, we will reveal the mechanisms by which
keratins become asymmetrically inherited (Aim 1) and can bias cell fate (Aim 2).
We will first test how interactions with proteins present at the apical cell cortex, and the dynamics of the filaments
inside the cell, control their asymmetric inheritance by outer cells during cell division. We will then determine how
keratins can regulate key aspects of cell mechanics and polarity to control the distribution of the key transcription
factors that specify trophectoderm fate.
In summary, in this proposal we will address a fundamental open question about the specification of the first
differentiated cell lineages during mammalian development, and unveil some of the first functions of keratin
intermediated filaments during early mammalian development, which unlike those of other cytoskeletal elements
like microtubules and actin, remain largely unknown.

## Key facts

- **NIH application ID:** 10378489
- **Project number:** 5R01HD102013-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Nicolas Plachta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $491,090
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378489

## Citation

> US National Institutes of Health, RePORTER application 10378489, Revealing how cytoskeletal dynamics form the early mammalian embryo (5R01HD102013-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10378489. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*