Polydactylous limbs in Strong’s Luxoid mice result from ectopic polarizing activity

Abstract

Strong's Luxoid (1stD) is a semidominant mouse mutation in which heterozygotes show preaxial hindlimb polydactyly, and homozygotes show fore- and hindlimb polydactyly. The digit patterns of these polydactylous limbs resemble those caused by polarizing grafts, since additional digits with posterior character are present at the anterior side of the limb. Such observations suggest that 1stD limb buds might contain a genetically determined ectopic region of polarizing activity. Accordingly, we show that mutant embryos ectopically express the pattern-determining genes fibroblast growth factor 4 (fgf-4), sonic hedgehog (shh), and Hoxd-12 in the anterior region of the limb. Further, we show that anterior mesoderm from mutant limbs exhibits polarizing activity when grafted into host chicken limbs. In contrast to an experimentally derived polydactylous transgenic mouse, forelimbs of homozygotes show a normal pattern of Hoxb-8 expression, indicating that the duplication of polarizing tissue here occurs downstream or independently of Hoxb-8. We suggest that the 1st gene product is involved in anteroposterior axis formation during normal limb development.

A mathematical framework for evo-devo dynamics

“…A mutant’s environmental trait i ∈ {1, …, N e } at age a ∈ {1, …, N a } is ϵ ia ∈ ℝ. Although we do not consider the developmental or evolutionary change of the number of traits (i.e., of N g , N p , or N e ), our framework still allows for the modelling of the developmental or evolutionary origin of novel traits (e.g., the origin of a sixth digit where there was five previously in development or evolution; Chan et al, 1995; Litingtung et al, 2002; Müller, 2010, or a gene duplication event) by implementing a suitable codification (e.g., letting x ia mean sixth-digit length, being zero in a previous age or evolutionary time; or by letting ỹ ia mean nucleotide presence and be zero for all novel loci before duplication).…”

“…A mutant’s phenotype i ∈ {1, …, N p } at age a ∈ {1, …, N a } is x ia ∈ R. Moreover, each individual has a number N e of environmental traits that describe her local environment at each age. A mutant’s environmental trait i ∈ {1, …, N e } at age a ∈ {1, …, N a } is ϵ ia ∈ ℝ.. We do not consider the developmental or evolutionary change of the number of traits (i.e., of N g , N p , or N e ), but our framework allows for the modeling of the developmental or evolutionary origin of novel traits (e.g., the origin of a sixth digit where there was five previously in development or evolution; Chan et al, 1995; Litingtung et al, 2002; Müller, 2010) by implementing a suitable codification (e.g., letting x ia mean sixth-digit length, being zero in a previous age or evolutionary time).…”

Spontaneous pre-axial polydactyly in Swiss mice

“…Polydactyly in mice can have dominant, semi-dominant or recessive inheritance depending on the affected gene -458 genotypes can be involved in it (MGI, 2020). The pre-axial phenotype is the most common one among spontaneous mutations; it has semi-dominant or recessive inheritance (GRÜNEBERG, 1942;CARTER, 1951, SEARLE 1964JOHNSON, 1967;CHAN et al, 1995;YADA et al, 2002).…”