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Mechanistic roles of the basement membrane mechanics in cellular morphodynamics and tissue patterning of the pre-gastrulating embryo

Award Number: F32HD105442
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary/Abstract Establishing proper tissue-level architecture and patterning during early embryogenesis is crucial for a successful pregnancy. A high rate of mortality seen in human embryos during the first 2-3 weeks post-fertilization is a major cause of early pregnancy loss, yet the essential cellular, molecular, and mechanical changes remain poorly defined. During early post-implantation mammalian embryogenesis, an extra-embryonic epithelial layer, the visceral endoderm, plays an essential role in the symmetry-breaking event that specifies the anterior- posterior patterning of the epiblast. Specifically, a subset of the visceral endoderm cells, the anterior visceral endoderm, migrates toward one end of the future anterior-posterior axis to pattern the epiblast. Recent work from our lab reveals that the embryonic basement membrane plays an essential role in symmetry breaking and morphogenesis that sets the stage for gastrulation. However, how the extracellular mechanics modulates the collective cellular dynamics and instructs cell identities for pattern formation remains not known. Here we propose to determine how the embryonic basement membrane coordinates the collective cell behaviors and facilitates anterior-posterior specification for pattern formation. First, we will comprehensively map the cell behaviors of the entire visceral endoderm with imaging approaches and define the role of the basement membrane in anterior visceral endoderm migration through genetic perturbations in stem cell-derived embryo- like structures as well as in the natural embryos. Next, we will map the basement membrane mechanics and apply a single-cell transcriptomics approach to generate in situ cell fate maps of the pre-gastrulating embryos. We will functionally test how the basement membrane mechanics regulate cell identities by correlating the gene expression profiles with basement membrane architecture and validate the findings with basement membrane- perturbed embryos. Finally, we will implement multi-scale mathematical models that integrate cell identities and cell dynamics with the basement membrane mechanics to uncover mechanisms of pattern formation. Overall, these experiments will unveil functional roles of the extraembryonic environment in defining the cell identities of the pre-gastrulation embryos. These findings will inform subsequent studies in my future goals on the conserved roles of the basement membrane and the extraembryonic tissues in topologically distinct embryos seen in human. Training during my fellowship period will expand my skillsets toward studying the more complex biology of mammals and broaden my knowledge on new aspects of developmental biology. The research environment at California Institute of Technology will further foster interdisciplinary collaborations that allow the development of novel approaches to investigate early mammalian embryogenesis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$50,703 )
2024	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	3	10/10/2023	NON-COMPETING CONTINUATION	-$50,703
														Subtotal = -$50,703

Issue Date FY: 2023 ( Subtotal = $76,052 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	3	3/21/2023	NON-COMPETING CONTINUATION	$76,052
														Subtotal = $76,052

Issue Date FY: 2022 ( Subtotal = $71,730 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	2	5/2/2022	NON-COMPETING CONTINUATION	$71,730
														Subtotal = $71,730

Issue Date FY: 2021 ( Subtotal = $68,562 )
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	3/5/2021	NEW	$68,562
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	1	3/5/2021	NEW	$0
														Subtotal = $68,562

Grand Total All Awards = $165,641

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Mechanistic roles of the basement membrane mechanics in cellular morphodynamics and tissue patterning of the pre-gastrulating embryo

Award Number: F32HD105442

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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