Spots and stripes: Pleomorphic patterning of stem cells via p-ERK-dependent cell chemotaxis shown by feather morphogenesis and mathematical simulation

Abstract

Summary A key issue in stem cell biology is the differentiation of homogeneous stem cells towards different fates which are also organized into desired configurations. Little is known about the mechanisms underlying the process of periodic patterning. Feather explants offer a fundamental and testable model in which multi-potential cells are organized into hexagonally arranged primordia and the spacing between primordia. Previous work explored roles of a Turing reaction-diffusion mechanism in establishing chemical patterns. Here we show that a continuum of feather patterns, ranging from stripes to spots, can be obtained when the level of p-ERK activity is adjusted with chemical inhibitors. The patterns are dose-dependent, tissue stage-dependent, and irreversible. Analyses show ERK-activity-dependent mesenchymal cell chemotaxis is essential for converting micro-signaling centers into stable feather primordia. A mathematical model based on short-range activation, long-range inhibition, and cell chemotaxis is developed and shown to simulate observed experimental results. This generic cell behavior model can be applied to model stem cell patterning behavior at large.

Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles

“…Further support for a key evolutionarily conserved role for Fgf20 signaling in epidermal appendage formation comes from the scaleless mutant chicken, which lacks almost all feathers and scales due to a nonsense mutation in Fgf20 (Wells et al 2012). In addition, in vitro studies have implicated Fgfs in dermal condensation formation in chicken dermis (Song et al 2004;Lin et al 2009).…”

Partial differential equations for self-organization in cellular and developmental biology

“…For their time, they were adequate in that the prevailing biological data were also at the macroscopic coarse-grained level. In fact, they can still be considered to be very useful paradigm models for patterning on the macroscopic scale, either alone or coupled together [22,60,97,98].…”

“…(a) mechanisms for axis formation, for example, left-right polarity initiation in the mouse [2][3][4]; (b) heterogeneous cell fate decisions, including the roles of Nodal and Lefty gene products in left-right polarity signal amplification [2,5], cell fates in the zebrafish mesoderm [6], the induction of neural tissue in the frog [1], patterning in the Drosophila wing [7] and hair follicle formation [8]; (c) controlled cell migrations, illustrated by gastrulation, lung morphogenesis and nervous system development [9][10][11]; (d) skeletal morphogenesis, for example the formation of somites [12,13] and limbs [14][15][16][17]; (e) the formation of skin patterns, typified by mammalian coat markings [18][19][20] and feather bud arrangements [21,22]; (f) fine-grained patterning, illustrated by lateral inhibition within delta-notch signalling [23]; (g) adhesion-driven cell sorting [24,25]. Figure 1 illustrates four examples of self-organization in developmental biology, including coat markings, limb/digit, somite and feather bud formation.…”

“…Examples include the formation of the gut (gastrulation) [10,11], lung morphogenesis [9] and feather bud formation [22]. In addition to modelling chemotaxis in development [76,77], such models are also commonly considered for coat marking patterns [78] and swarming microbe motility [28][29][30].…”

Regulatory Differences in Natal Down Development between Altricial Zebra Finch and Precocial Chicken

“…In feather development, the MAPK signaling pathway was shown to be the major downstream pathway in response to FGFs (Lin et al 2009). Moreover, knockout of the key component of the MAPK pathway reduced epithelium thickness in mouse (Scholl et al 2007).…”