Allocation of distinct organ fates from a precursor field requires a shift in expression and function of gene regulatory networks

Abstract

A common occurrence in metazoan development is the rise of multiple tissues/organs from a single uniform precursor field. One example is the anterior forebrain of vertebrates, which produces the eyes, hypothalamus, diencephalon, and telencephalon. Another instance is the Drosophila wing disc, which generates the adult wing blade, the hinge, and the thorax. Gene regulatory networks (GRNs) that are comprised of signaling pathways and batteries of transcription factors parcel the undifferentiated field into discrete territories. This simple model is challenged by two observations. First, many GRN members that are thought to control the fate of one organ are actually expressed throughout the entire precursor field at earlier points in development. Second, each GRN can simultaneously promote one of the possible fates choices while repressing the other alternatives. It is therefore unclear how GRNs function to allocate tissue fates if their members are uniformly expressed and competing with each other within the same populations of cells. We address this paradigm by studying fate specification in the Drosophila eye-antennal disc. The disc, which begins its development as a homogeneous precursor field, produces a number of adult structures including the compound eyes, the ocelli, the antennae, the maxillary palps, and the surrounding head epidermis. Several selector genes that control the fates of the eye and antenna, respectively, are first expressed throughout the entire eye-antennal disc. We show that during early stages, these genes are tasked with promoting the growth of the entire field. Upon segregation to distinct territories within the disc, each GRN continues to promote growth while taking on the additional roles of promoting distinct primary fates and repressing alternate fates. The timing of both expression pattern restriction and expansion of functional duties is an elemental requirement for allocating fates within a single field.

Variation in Pleiotropic Hub Gene Expression Is Associated with Interspecific Differences in Head Shape and Eye Size in Drosophila

“…2017 ) and later they play a pivotal role in retinal specification ( Treisman 2013 ; Casares and Almudi 2016 ). These distinct roles have been suggested to be achieved by considerable rewiring of the respective GRNs, which allows them to fulfill temporally and even spatially restricted tasks ( Palliyil et al. 2018 ).…”

A multi-gene knockdown approach reveals a new role for Pax6 in controlling organ number in Drosophila

“…The ey-GAL4 was generated by fusing the first intron of the ey gene (which contains an eye-specific enhancer) to GAL4 (Hauck et al, 1999). Both lines are initially expressed broadly throughout the entire disc, but by the second larval instar ey-GAL4 expression becomes restricted to the eye field whereas DE-GAL4 is confined to the dorsal half of the eye disc (Hauck et al, 1999;Kumar and Moses, 2001;Morrison and Halder, 2010;Palliyil et al, 2018).…”

“…Imaginal discs were prepared, viewed on a Zeiss Axioplan II compound fluorescence microscope, and photographed as described by Spratford and Kumar (2014). Adult samples were prepared, viewed with a scanning electron microscope or a Zeiss Discovery microscope, and photographed as described by Palliyil et al (2018).…”

“…The view that these Pax6 genes play limited roles in the eyeantennal disc has been recently challenged by our demonstrations that Ey and Toy also function to control growth of the entire eyeantennal disc and to prevent the developing eye from being reprogrammed into a wing (Zhu et al, 2017;2018;Palliyil et al, 2018). These functions were discovered under circumstances in which multiple genes are simultaneously removed from the disc.…”

“…These functions were discovered under circumstances in which multiple genes are simultaneously removed from the disc. For example, a role for these transcription factors in promoting growth of the entire disc was revealed only when we removed both Pax6 genes simultaneously or in combination with the zinc-finger transcription factor Teashirt (Tsh) (Zhu et al, 2017;Palliyil et al, 2018). Similarly, the unexpected finding that Ey and Toy are required to prevent the eye from transforming into a wing is only seen when either Pax6 gene is simultaneously downregulated alongside members of the Polycomb Group (PcG) of epigenetic repressors (Zhu et al, 2018).…”