Biology subjects

Cohn, M. J.

Publications and source records attributed to Cohn, M. J..

4 recordsLinked to original sources

bioRxiv2025

Identification of non-coding elements associated with the evolutionary loss of digit 1.

Evolutionary loss of digits and limbs occurred many times during the diversification of tetrapods. The limbs of the earliest tetrapods were polydactylous, bearing as many 8 digits, but after the pentadactyly (five digits) was stabilized, no lineage evolved more than five digits per limb but many underwent digit loss. Within mammals, digit 1 (thumb on the forelimb or hallux on the hindlimb) is lost most frequently and is typically the first digit to disappear. Evidence from numerous studies of limb development shows that digit 1 development is controlled by mechanisms that are at least partially independent of the posterior 4 digits. In addition, evolutionary loss of digit 1 occurred independently in forelimbs and hindlimbs. Despite the frequency of digit loss in mammals, the underlying genetic mechanisms have not been uncovered. We used comparative genomics and bioinformatics to reconstruct the evolutionary history of genomic changes associated with digit 1 loss in the forelimbs and/or hindlimbs of 65 mammalian species. We identified a set of conserved non-coding elements that evolved in concert with independent (parallel) losses of digit 1. These elements, which are frequently near genes with known roles in digit development, underwent accelerated evolution in digit-reduced lineages. Furthermore, we find that elements with accelerated rates of evolution show significant loss of binding sites for transcription factors that are crucial for anterior digit development. The results suggest that cis-regulatory elements important for the development of digit 1 are evolutionarily accelerated in mammalian lineages that underwent reduction and loss of digit 1.

evolutionary biology↗

bioRxiv2025

Endoderm differentiates into a transient epidermis in the mouse perineum

In eutherian mammals, the embryonic cloaca is partitioned into genitourinary and anorectal canals by the urorectal septum. At the caudal end of the mouse embryo, the urorectal septum contributes to the perineum, which separates the anus from the external genitalia. Growth of the urorectal septum displaces cloacal endoderm to the surface of the perineum, where it is incorporated into epidermis, an enigmatic fate for endodermal cells. Here we show that endodermal cells differentiate into true epidermis in the perineum, expressing basal, spinous, and granular cell markers. Endodermal epidermis is lost through terminal differentiation and desquamation postnatally, when it is replaced by ectoderm. Live imaging and single-cell tracking reveal that ectodermal cells move at a faster velocity in a lateral-to-medial direction, converging towards the narrow band of endoderm between the anus and external genitalia. Although the perineum is sexually dimorphic, similar spatiotemporal patterns of cell movement were observed in males and females. These results demonstrate that cloacal endoderm differentiates into a non-renewing, transient epidermis at the midline of the perineum. Differential movement of endodermal and ectodermal cells suggests that perineum epidermis develops by convergent extension. These findings provide a foundation for further studies of perineum development and of sex-specific epidermal phenotypes.

developmental biology↗

bioRxiv2020

Anomalous incisor morphology indicates tissue-specific roles for Tfap2a and Tfap2b in tooth development

Mice possess two types of teeth that differ in their cusp patterns; incisors have one cusp and molars have multiple cusps. The patterning of these two types of teeth relies on fine-tuning of the reciprocal molecular signaling between dental epithelial and mesenchymal tissues during embryonic development. Here we show that the incisors are populated only at early time points by the neural crest, whereas the molars continue to receive contributions at later stages, revealing a temporal difference that could alter epithelial-mesenchymal signaling dynamics between these two types of teeth. The AP-2 transcription factors, particularly Tfap2a and Tfap2b, are essential components of such epithelial-mesenchymal signaling interactions that coordinate craniofacial development in mice and other mammals, but little is known about their roles in the regulation of tooth development and shape. We demonstrate that incisors and molars differ in their temporal and spatial expression of Tfap2a and Tfap2b; in particular, at the bud stage, Tfap2a is expressed in both the epithelium and mesenchyme of the incisors and molars but expression of Tfap2b is restricted to the mesenchyme of the molars. Tissue-specific deletions show that loss of the epithelial domain of Tfap2a and Tfap2b affects the number and spatial arrangement of the incisors, notably resulting in duplicated lower incisors. In contrast, deletion of these two genes in the mesenchymal domain has little effect on tooth development. Collectively these results implicate epithelial expression of Tfap2a and Tfap2b in dorsal-ventral patterning of the incisors and suggest that these genes contribute to morphological differences between anterior (incisor) and posterior (molar) teeth within the mammalian dentition. HighlightsO_LILate-migrating cranial neural crest cells contribute extensively to the developing molar tooth germs but minimally to the incisors. C_LIO_LIDuring tooth development, transcription factors Tfap2a and Tfap2b are expressed in spatially and temporally dynamic patterns and differ between incisor and molar tooth germs. C_LIO_LIEpithelial expression of Tfap2a and Tfap2b is necessary for incisor development, but mesenchymal expression of these genes is not required. C_LI

developmental biology↗

bioRxiv2018

Evolution of limb development in cephalopod mollusks

Cephalopod mollusks evolved numerous anatomical innovations, including specialized arms and tentacles, but little is known about the developmental mechanisms underlying the evolution of cephalopod limbs. Here we show that all three axes of cuttlefish limbs are patterned by the same signaling networks that act in vertebrates and arthropods, although they evolved limbs independently. In cuttlefish limb buds, Hedgehog is expressed anteriorly. Posterior transplantation of Hedgehog-expressing cells induced mirror-image limb duplications. Bmp and Wnt signaling, which establishes dorsoventral polarity in vertebrate and arthropod limbs, is similarly polarized in cuttlefish. Inhibition of the dorsal Bmp signal caused ectopic expression of Notum, a ventral sucker field marker, and development of ectopic suckers. Cuttlefish limbs also show proximodistally regionalized expression of Htx, Exd, Dll, Dac, Sp8/9, and Wnt genes, which delineate arm and tentacle sucker fields. These results suggest that cephalopod limbs evolved by parallel activation of an ancient genetic program for appendage development that was present in the bilaterian common ancestor.

developmental biology↗