Montague, T. G. | Search bioRxiv

bioRxiv2022

A brain atlas of the camouflaging dwarf cuttlefish, Sepia bandensis

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied marine mollusks that exhibit an array of interesting biological phenomena, including dynamic camouflage, complex social behaviors, prehensile regenerating arms, and large brains capable of learning, memory, and problem-solving [1-10]. The dwarf cuttlefish, Sepia bandensis, is a promising model cephalopod species due to its small size, substantial egg production, short generation time, and dynamic social and camouflage behaviors [11]. Cuttlefish dynamically camouflage to their surroundings by changing the color, pattern and texture of their skin. Camouflage is optically-driven, and is achieved by expanding and contracting hundreds of thousands of pigment-filled saccules (chromatophores) in the skin, which are controlled by motor neurons emanating from the brain. We generated a dwarf cuttlefish brain atlas using magnetic resonance imaging (MRI), deep learning, and histology, and we built an interactive web tool (cuttlebase.org) to host the data. Guided by observations in other cephalopods [12-20], we identified 32 brain lobes, including two large optic lobes (75% the total volume of the brain), chromatophore lobes whose motor neurons directly innervate the chromatophores of the color-changing skin, and a vertical lobe that has been implicated in learning and memory. This brain atlas provides a valuable tool for exploring the neural basis of cuttlefish behavior.

neuroscience↗

bioRxiv2021

Regulation of Vg1 biogenesis during mesendoderm induction

The TGF-beta signals Vg1 (Dvr1/Gdf3) and Nodal form heterodimers to induce vertebrate mesendoderm. The Vg1 proprotein is a monomer retained in the endoplasmic reticulum (ER) and is processed and secreted upon heterodimerization with Nodal, but the mechanisms underlying Vg1 biogenesis are largely elusive. Here we clarify the mechanisms underlying Vg1 retention, processing, secretion and signaling, and introduce a Synthetic Processing (SynPro) system that enables the programmed cleavage of ER-resident and extracellular proteins. First, we find that Vg1 can be processed by intra- or extracellular proteases. Second, Vg1 can be processed without Nodal but requires Nodal for secretion and signaling. Third, Vg1-Nodal signaling activity requires Vg1 processing, whereas Nodal can remain unprocessed. Fourth, Vg1 employs exposed cysteines, glycosylated asparagines, and BiP chaperone-binding motifs for monomer retention in the ER. These observations suggest two mechanisms for rapid mesendoderm induction: chaperone-binding motifs help store Vg1 as an inactive but ready-to-heterodimerize monomer in the ER, and the flexibility of Vg1 processing location allows efficient generation of active heterodimers both intra- and extracellularly. These results establish SynPro as a new in vivo processing system and define molecular mechanisms and motifs that facilitate the generation of active TGF-beta heterodimers. SignificanceThe TGF-beta family members Nodal and Vg1 are the major inducers of mesendoderm formation during vertebrate embryogenesis. We previously established that the Vg1 proprotein is retained in the endoplasmic reticulum (ER), and that Nodal and Vg1 form heterodimers to pattern the early embryo. However, the mechanisms underlying the retention, processing, secretion, and signaling of Vg1 have been unclear. We found two mechanisms that embryos use to efficiently generate active Nodal-Vg1 heterodimers: (1) Vg1 employs its chaperone-binding motifs to ensure its retention as a ready-to-heterodimerize monomer in the ER; (2) Using a newly devised Synthetic Processing (SynPro) System, we found that Vg1 must be processed for signaling to occur, but its processing location is flexible.

developmental biology↗