Temporal loss of En1 during limb development causes distinct phenotypes

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Proper organogenesis relies on precise spatiotemporal gene regulation.
• Engrailed-1 (En1) is vital for dorsal-ventral patterning in mouse limb development (embryonic days 9.5-11.5).

Purpose of the Study:

• To identify regulatory elements controlling En1 expression during mouse limb development.
• To understand the roles of Maenli and LSEE1&2 in coordinating En1 expression waves for limb patterning.

Main Methods:

• Identification of intergenic enhancer elements (LSEE1&2).
• Analysis of Maenli and LSEE1&2 function in En1 expression.
• Assessment of developmental phenotypes resulting from loss of Maenli or LSEE1&2.

Main Results:

• Discovered LSEE1&2 enhancers essential for En1 expression at E10.5 and E11.5.
• Demonstrated Maenli and LSEE1&2 coordinate two temporal waves of En1 expression.
• Showed distinct phenotypes arise from Maenli versus LSEE1&2 loss, impacting axial patterning genes.

Conclusions:

• Maenli and LSEE1&2 orchestrate sequential En1 expression waves for dorsal-ventral limb identity.
• Temporal cis-regulatory elements modulate lineage specification and developmental patterning via spatiotemporal gene function.