Chapter 3 - Leveraging neural crest pluripotency to extend retinal and craniofacial niches for building neurovascular organoids—a theranostic and drug development perspective

Abstract

The neural crest cells (NCCs) arising from the prosencephalon, mesencpehalon, and rhombencephalon make up the cranial neural crest cells that collectively participate in the formation of frontonasal process, pharyngeal arches (that contribute to the craniofacial skeleton, connective tissue), and also the periocular mesenchyme. The periocular NCCs (pNCCs) make important contributions during the optic cup patterning and the optic fissure closure and are derived from diencephalon and the anterior mesencephalon migrating dorsoventrally to the optic cup and anteriorly to the codeveloping frontonasal process. The developmental proximity indicates room for building novel regenerative platforms for craniofacial organoids and refining the existing ocular disease modeling approaches, by employing pNCCs to generate more robust in vitro ocular organoids, or skewing ectodermal patterning protocols towards pNCCs to generate robust ocular and craniofacial or hybrid organoids for studying the craniofacial and ocular defects seen in many congenital NCC developmental disorders or the cranial neurocristopathies. The chapter broadly speaks about various ocular organoids, with a focus on leveraging neural crest contributions for redesigning retinal organoid systems for retinal degenerative diseases, we have also briefly touched upon the scope of NCCs for regenerating corneal nerves and a few other organoid systems such as lung, gut and tumor organoids beyond the scope of the topic, to discuss some very recent developments that we believe are worthwhile due their pathbreaking and novel findings, which could be applied and translated to organoid model systems across the board.