Search

Fat and Dachsous are evolutionarily conserved atypical cadherins that regulate polarized cell behaviors. In the Drosophila wing, they interact heterophilically between neighboring cells, localize asymmetrically to opposite cell ends, and control wing shape by regulating oriented cell rearrangements and divisions. Fat and Dachsous have 34 and 27 cadherin repeats, respectively, and previous work has identified trans interactions between their first four cadherin repeats. Here, we identify a second heterophilic binding site in their C-terminal cadherin repeats and show the conservation of this binding site in human Fat4 and Dachsous1. We provide evidence that both N- and C-terminal binding sites regulate the stability of Fat-Dachsous binding interactions and show that the N-terminal binding sites are partly dispensable for Fat-Dachsous function in vivo. Finally, we provide in vivo confirmation that the N-terminal repeats interact in an anti-parallel manner. We propose that multiple binding sites promote the clustering of Fat and Dachsous into a lattice-like array., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

Planar polarity describes the coordinated polarization of cells within a tissue plane, and in animals can be determined by the "core" or Fat-Dachsous pathways. Current models for planar polarity establishment involve two components: tissue-level "global" cues that determine the overall axis of polarity and cell-level feedback-mediated cellular polarity amplification. Here, we investigate the contributions of global cues versus cellular feedback amplification in the core and Fat-Dachsous pathways during Drosophila pupal wing development. We present evidence that these pathways generate planar polarity via distinct mechanisms. Core pathway function is consistent with strong feedback capable of self-organizing cell polarity, which can then be aligned with the tissue axis via weak or transient global cues. Conversely, generation of cell polarity by the Ft-Ds pathway depends on strong global cues in the form of graded patterns of gene expression, which can then be amplified by weak feedback mechanisms., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

The hypothalamus regulates many innate behaviors, but its development remains poorly understood. Here, we used single-cell RNA sequencing (RNA-seq) and hybridization chain reaction (HCR) to profile multiple stages of early hypothalamic development in the chick. Hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations then emerge and give rise to tuberal and mammillary/paraventricular hypothalamic cells. At later stages, the regional organization of the chick and mouse hypothalamus is highly similar. We identify selective markers for major subdivisions of the developing chick hypothalamus and many previously uncharacterized candidate regulators of hypothalamic induction, regionalization, and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that prethalamus-derived follistatin inhibits hypothalamic induction. This study clarifies the organization of the nascent hypothalamus and identifies molecular mechanisms that may control its induction and subsequent development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) more...