Hyperbranched polymers (HBPs), an important subclass of dendritic macromolecules, are highly branched, three-dimensional globular nanopolymeric architectures. Attractive features like highly branched topological structures, adequate spatial cavities, numerous terminal functional groups and convenient synthetic procedures distinguish them from the available polymers (the linear, branched, and crosslinking polymers). Due to their unique physical/chemical properties, applications of HBPs have been explored in a large variety of fields. In particular, HBPs exhibit unique advantages in the biological and biomedical systems and devices. Firstly, the way to prepare HBPs usually only involves simple one-pot reactions and avoids the complicated synthesis and purification procedures, which makes the manufacturing process more convenient, thus reducing production costs. Secondly, the large number of end-groups of HBPs provides a platform for conjugation of the functional moieties and can also be employed to tailor-make the properties of HBPs, enhancing their versatility in biological applications. Thirdly, HBPs possess excellent biocompatibility and biodegradability, controlled responsive nature, and ability to incorporate a multiple array of guest molecules through covalent or noncovalent approaches. All of these features of HBPs are of great significance for designing and producing biomaterials. To date, significant progress has been made for the HBPs in solving some of the fundamental and technical questions toward their bioapplications. The present review highlights the contribution of HBPs to biological and biomedical fields with intent to aid the researchers in exploring HBPs for bioapplications.

Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/β-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/β-catenin signaling pathway during lip formation and fusion. By contrast, a `fusion-resistant'gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/β-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.

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The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1.

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The three-dimensional structures of hyperbranched materials have made them attractive in many important applications. However, the preparation of hyperbranched materials remains challenging. The hyperbranched materials from addition polymerization have gained attention, but are still confined to only a low level of branching and often low yield. Moreover, the complication of synthesis only allows a few specialized monomers and inimers to be used. Here we report a 'Vinyl Oligomer Combination' strategy; a versatile approach that overcomes these difficulties and allows facile synthesis of highly branched polymeric materials from readily available multi-vinyl monomers, which have long been considered as formidable starting materials in addition polymerization. We report the alteration of the growth manner of polymerization by controlling the kinetic chain length, together with the manipulation of chain growth conditions, to achieve veritable hyperbranched materials, which possess nearly 70% branch ratios as well as numerous vinyl functional groups.

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The specification of the intricate neuronal assemblies that characterize the forebrain is not well understood. The ventral spinal cord is specified through a concentration gradient of Sonic hedgehog (Shh) protein secreted by the notochord. Shh is expressed also in the forebrain neuroepithelium (neural Shh) and the underlying notochord and prechordal plate. Neural Shh is essential for the development of the prethalamus (ventral thalamus), but its effects on the thalamus (dorsal thalamus) are still unclear. We hypothesized that neural Shh would act on a previously regionalized dorsal diencephalic region to promote the emergence of specific thalamic nuclear and histological traits. To find out, we generated a conditional mouse mutant line specifically lacking Shh expression in the diencephalic neuroepithelium. We show that the transcription factor Gbx2, required for thalamic development downstream Shh, is expressed in our mutant in a restricted thalamic region and is necessary and sufficient for the differentiation of the medial and intralaminar thalamic nuclei. In the rest of the thalamus, neural Shh is required to promote neuronal aggregation into nuclei as well as axonal extension. In this way, the individual thalamic nuclei show differential dependence on Shh, Gbx2, or both for their differentiation. Additionally, Gbx2 is required for the survival of thalamic neurons.