Biology subjects

Waas, B.

Publications and source records attributed to Waas, B..

4 recordsLinked to original sources

bioRxiv2025

Patterns of Mitochondrial ATP Predict Tissue Folding

The construction of complex tissue shapes during embryonic development results from spatial patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during morphogenesis. Specifically, mitochondria are locally enriched at the apical sides of epithelial cells during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Timelapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase in epithelial cells prior to actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apicobasal patterning are conserved during apical constriction in flies, chicks, and mice, and these subcellular patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in embryonic development.

developmental biology↗

bioRxiv2024

KIF3C Regulates Bergmann Glia Density and Patterning during Cerebellar Development

Kinesin-2 motors have been demonstrated to regulate Hedgehog (HH) signaling, particularly within the developing cerebellum (Spassky et al., 2008; Waas et al., 2024). KIF3A/KIF3B are required for ciliogenesis in mice, and loss of this motor complex results in cerebellar hypoplasia due to lack of mitogenic response of HH-responsive cerebellar granule neural progenitors (CGNPs). Homodimeric KIF17 regulates HH-dependent CGNP proliferation through regulating levels of SHH and GLI3 but is not required for ciliogenesis in the developing cerebellum. Germline deletion of Kif3c has previously been reported to have no effect on embryonic development or gross cerebellar morphology in adult mice (Yang et al., 2001). Examination of these mice during neonatal development reveal cerebellar hypoplasia due to reduced CGNP proliferation in Kif3c mutant mice. While decreased CGNP proliferation is often associated with reduced Hedgehog (HH) signaling, we did not detect a change in the levels of HH signaling in Kif3c-/- cerebella. However, we observed Bergmann glia density and localization is altered in Kif3c mutants, a phenotype consistent with disrupted Notch signaling. Further, we detected reduced expression of Hes1 in Kif3c-/- cerebella. Altogether, these data demonstrate KIF3C is required for proper cerebellar development but in a HH-independent manner. HighlightsO_LIKif3c is widely expressed in developing cerebellum C_LIO_LIKIF3C regulates cerebellar size, but in a HH-independent manner C_LIO_LIKif3c-/- mice have increased BG density and abnormal spatial patterning C_LI

developmental biology↗

bioRxiv2022

Dual and Opposing Roles for the Kinesin-2 Motor, KIF17, in Hedgehog-dependent Cerebellar Development

While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where Kif17 is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline Kif17 deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein. Notably, Purkinje cell-specific Kif17 deletion phenocopies Kif17 germline mutants. Surprisingly, CGNP-specific Kif17 deletion results in the opposite phenotype- increased CGNP proliferation and HH target gene expression due to altered GLI transcription factor processing. Together these data identify KIF17 as a key regulator of HH-dependent cerebellar development, with dual and opposing roles in HH-producing Purkinje cells and HH-responding CGNPS. TeaserDuring cerebellar development, the KIF17 microtubule motor performs opposing roles in HH-producing and HH-responding cells.

developmental biology↗

bioRxiv2018

Acute inhibition of heterotrimeric kinesin-2 function reveals mechanisms of intraflagellar transport in mammalian cilia

The trafficking of components within cilia, called intraflagellar transport (IFT), is powered by kinesin-2 and dynein-2 motors. Loss of function in any subunit of the heterotrimeric KIF3A/KIF3B/KAP kinesin-2 motor prevents ciliogenesis in mammalian cells and has hindered an understanding of how kinesin-2 motors function in IFT. We used a chemical-genetic approach to engineer an inhibitable KIF3A/KIF3B (i3A/i3B) kinesin-2 motor that is capable of rescuing WT motor function in Kif3a/Kif3b double-knockout cells. Inhibitor addition blocks ciliogenesis or, if added to ciliated cells, blocks IFT within two minutes, which leads to a complete loss of primary cilia within six hours. The kinesin-2 family members KIF3A/KIF3C and KIF17 cannot rescue ciliogenesis in Kif3a/Kif3b double-knockout cells nor delay the disassembly of full-formed cilia upon i3A/i3B inhibition. These data suggest that KIF3A/KIF3B/KAP is the sole and essential motor for cilia assembly and function in mammalian cells, indicating a species-specific adaptation of kinesin-2 motors for IFT function.

cell biology↗