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EDGE CMT: Neural cell type evolution in insect retinas

Award Number: R01HG013634
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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EDGE CMT: Neural cell type evolution in insect retinas - PROJECT SUMMARY (See instructions): Overview: Animal genomes provide instructions for producing an amazing diversity of cell types during development, perhaps especially in the brain. One of the most surprising findings in the genome-sequencing era has been how few genes there are - only about 25,000 in most animal genomes regardless of their size or complexity. How do these genes interact during development to produce the incredible diversity of cell types? What kinds of genetic changes have allowed neural cell types to be modified or to increase in number across species over evolutionary time? In order to address such questions, we propose to use the insect retina as a model to understand the genetic basis of neural cell type evolution. Insect eyes can be incredibly diverse in some ways and yet rigidly conserved in others. Compound eyes are highly recognizable given their characteristic structure. Yet these structures can vary in morphology and underlying organization in sometimes dramatic ways to help adapt insects to thrive in diverse environments around the world. For example, butterflies have expanded color vision using a more complex retinal mosaic, while house flies have a novel neural type that improves target detection and tracking. Hidden underneath the surface, mosquito eyes have dramatically rearranged and highly regionalized retinas, potentially for host and water detection. We present preliminary data which suggests that, overall, insect eye patterning is incredibly highly conserved and uses the same transcription factors and signaling pathways to define core cell types across species. This begs the question: What kinds of genetic changes underlie the dramatic differences found in some groups? How does this deeply conserved, highly organized feature evolve modified or novel functions? We will use a combination of new genomic and genetic tools such as single cell sequencing and CR IPSR/Cas9 genome editing to characterize differences across species, test the function of candidate genes directly in species of interest, and to identify and test gene regulatory regions responsible for neural cell type evolution. We will uncover how gene regulatory networks can be modified to reorganize tissues and to produce novel types of eel Is. Intellectual Merit: The Drosophila retina has been a premier model for the study of cell fate specification for many years. Now, new tools have opened the door to asking questions about how this exquisitely patterned structure evolves across species. The field is primed to understand how genetic networks specify an incredible diversity of neural fates and how changes in genome sequence shape that diversity. Our comparative approach will determine how the insect visual system has been modified over time in response to natural and sexual selection to produce new arrangements, modified functions, and novel types of neurons. Key questions include: 1) What types of genes are responsible for neural cell type evolution, and how are changes in their expression achieved? 2) How do novel neural types arise, increasing neural complexity? 3) How are deeply conserved developmental processes modified or added to without disrupting core ancestral function? 4) How do such changes influence animal behavior? We will identify fundamental principles by which processes such as cell fate specification evolve. This research will enhance our understanding of the evolution of complex traits and has broad implications for understanding how the genome encodes neural diversity and function. Broader Impacts: Using butterflies as a charismatic means of engagement, this project will enable educational activities at three levels: Citizen Science, 5th-12th graders, and undergraduate students. 1) Citizen Science research will engage dozens of regional students and adults annually in collaboration with the San Diego Botanic Garden and the UC Reserve System. This project will use group butterfly walks at the Gardens and at Sc


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: 2026 ( Subtotal = $316,350 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Human Genome Research	000	3	8/6/2026	NON-COMPETING CONTINUATION	$316,350
														Subtotal = $316,350

Issue Date FY: 2025 ( Subtotal = $324,375 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Human Genome Research	000	2	9/17/2025	NON-COMPETING CONTINUATION	$324,375
														Subtotal = $324,375

Issue Date FY: 2024 ( Subtotal = $328,117 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Human Genome Research	000	1	9/1/2024	NEW	$328,117
														Subtotal = $328,117

Grand Total All Awards = $968,842

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EDGE CMT: Neural cell type evolution in insect retinas

Award Number: R01HG013634

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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